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Investigations into the mechanism of vasoconstrictor action of the topical steroid betamethasone‐17‐valerate in the rat
Author(s) -
Ahluwalia A.,
Flower R.J.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb12838.x
Subject(s) - bradykinin , captopril , pharmacology , vasodilation , betamethasone , chemistry , angiotensin converting enzyme , endocrinology , medicine , receptor , blood pressure
1 The effect of topical betamethasone upon skin blood flow was investigated in the rat. Two types of vasodilator stimuli were used; local heating to the surface of the skin and intradermal application of inflammatory agents. Blood flow was measured by laser doppler velocimetry. 2 Topical betamethasone‐17‐valerate (1 g with an 18 h pretreatment) significantly inhibited the heat‐induced vasodilatation in the rat skin, as also did systemically administered betamethasone (1 mg kg −1 , 3 h pretreatment). 3 Angiotensin converting enzyme (ACE) inhibitors (captopril, 5 mg kg −1 and enalapril, 1 mg kg −1 , 30 min pretreatments) were the only drugs out of several different types of systemically administered inhibitors and antagonists that were tested which also inhibited the heat‐induced vasodilatation. Aprotinin (100,000 KIU kg −1 , 5 min pretreatment) a serine protease inhibitor, significantly potentiated the heat‐induced response. 4 Bradykinin (50 nmol per site), des‐Arg 9 ‐bradykinin (5 nmol per site), substance P (0.1 nmol per site) and capsaicin (1 μmol per site) induced an increase in skin blood flow. 5 Topical betamethasone treatment resulted in a significant inhibition of the vasodilator response to des‐Arg 9 ‐bradykinin, whereas captopril treatment inhibited the responses to substance P, capsaicin, bradykinin and des‐Arg 9 ‐bradykinin. 6 Intradermal application of captopril (10–100 μg) also caused a dose‐dependent inhibition of the heat‐induced vasodilatation. 7 These results suggest that topical betamethasone may be acting in a manner similar to that of the ACE inhibitors to produce an inhibition of the flow responses in the skin and that this effect may be brought about by interfering with the action of vasodilator peptide(s) or protein(s).